BACKGROUND: Patients with heart failure (HF) with mildly reduced or preserved ejection fraction face heightened long-term risks of morbidity and mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the nonsteroidal mineralocorticoid receptor antagonist finerenone have both been shown to reduce the risk of cardiovascular events in this population, but the effects of their combined use are not known. METHODS: FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction ≥40%. Baseline SGLT2i use was a prespecified subgroup. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. We first assessed for evidence of treatment heterogeneity on the basis of baseline SGLT2i use. We further examined SGLT2i uptake during the trial and evaluated the treatment effects of finerenone accounting for baseline and during-trial use of SGLT2i in time-varying analyses. RESULTS: Among 6001 participants, 817 (13.6%) were treated with an SGLT2i at baseline. During 2.6 years median follow-up, treatment with finerenone similarly reduced the risk of the primary outcome in participants treated with an SGLT2i (rate ratio, 0.83 [95% CI, 0.60–1.16]) and without an SGLT2i at baseline (rate ratio, 0.85 [95% CI, 0.74–0.98]; P _interaction =0.76). In follow-up, 980 participants initiated SGLT2i, which was less frequent in the finerenone arm compared with placebo (17.7% versus 20.1%; hazard ratio, 0.86 [95% CI, 0.76–0.97]). Time-updated analyses accounting for baseline and subsequent use of SGLT2i did not meaningfully alter the treatment effects of finerenone on the primary end point. CONCLUSIONS: The treatment benefits of the nonsteroidal mineralocorticoid receptor antagonist finerenone were observed irrespective of concomitant use of an SGLT2i. These data suggest that the combined use of SGLT2i and a nonsteroidal mineralocorticoid receptor antagonist may provide additive protection against cardiovascular events in patients with HF with mildly reduced or preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04435626.

BACKGROUND: The effects of treatments for heart failure (HF) may vary among patients according to left ventricular ejection fraction (LVEF). In FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure), the nonsteroidal mineralocorticoid receptor antagonist finerenone reduced the risk of cardiovascular death and total worsening HF events in patients with HF with mildly reduced or preserved ejection fraction. We examined the effect of finerenone according to LVEF in FINEARTS-HF. METHODS: FINEARTS-HF was a randomized, placebo-controlled trial examining the efficacy and safety of finerenone in patients with HF and LVEF ≥40%. The treatment effect of finerenone was examined in prespecified analyses according to LVEF categories (<50%, ≥50% to <60%, and ≥60%) and with LVEF as a continuous variable. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. RESULTS: Baseline LVEF data were available for 5993 of the 6001 participants in FINEARTS-HF. Mean and median LVEF were 53±8% and 53% (interquartile range, 46%–58%), respectively. LVEF was <50% in 2172 (36%), between 50% and <60% in 2674 (45%), and ≥60% in 1147 (19%). Patients with higher LVEF were older, were more commonly female, were less likely to have a history of coronary artery disease, and more frequently had a history of hypertension and chronic kidney disease compared with those with a lower LVEF. Finerenone reduced the risk of cardiovascular death and total HF events consistently across LVEF categories (LVEF <50% rate ratio, 0.84 [95% CI, 0.68–1.03]; LVEF ≥50% to <60% rate ratio, 0.80 [0.66–0.97]; and LVEF ≥60% rate ratio, 0.94 [0.70–1.25]; P _interaction =0.70). There was no modification of the benefit of finerenone across the range of LVEF when analyzed as a continuous variable ( P _interaction =0.28). There was a similar consistent effect of finerenone on reducing the total number of worsening HF events (continuous P _interaction =0.26). CONCLUSIONS: In patients with HF with mildly reduced or preserved ejection fraction, finerenone reduced the risk of cardiovascular death and worsening HF events, irrespective of LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04435626. URL: https://eudract.ema.europa.eu ; Unique identifier: 2020-000306-29.

Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness. However, factors associated with mental illness are unclear. To synthesise and evaluate all available evidence on factors associated with depression, anxiety, and severe mental illness (SMI) among adults with AE or psoriasis. We searched electronic databases, grey literature databases, and clinical trial registries from inception to February 2022 for studies in adults with AE or psoriasis. Eligible studies were randomised controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety, or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesised results narratively, and if at least two studies were sufficiently homogenous, we pooled effect estimates in a random-effects meta-analysis. We included 21 studies (11 observational, 10 RCT). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety – one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest being female, and psoriatic arthritis, were associated with depression (female sex:OR = 1.62,95%CI = 1.09-2.40,95%PI = 0.62-4.23, I² = 24.90%, Tau² = 0.05; psoriatic arthritis:OR = 2.26,95%CI = 1.56-3.25,95%PI = 0.21-24.23, I² = 0.00%, Tau² = 0.00) and anxiety (female sex:OR = 2.59,95%CI = 1.32-5.07,95%PI = 0.00-3956.27, I² = 61.90%, Tau² = 0.22; psoriatic arthritis:OR = 1.98,95%CI = 1.33-2.94, I² = 0.00%, Tau² = 0.00). Moderate/severe psoriasis was associated with anxiety (OR = 1.14,95%CI = 1.05-1.25, I² = 0.00%, Tau² = 0.00), but not depression. Evidence from RCTs suggested adults with AE or psoriasis given placebo had higher depression and anxiety scores compared to comparators given targeted treatment (e.g., biologic agents). Our review highlights limited existing research on factors associated with depression, anxiety, and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared to skin disease treated with targeted therapy, however, follow-up was limited, therefore long-term effects on mental health are unclear.

Long COVID is the patient-coined term for the persistent symptoms of COVID-19 illness for weeks, months or years following the acute infection. There is a large burden of long COVID globally from self-reported data, but the epidemiology, causes and treatments remain poorly understood. Primary care is used to help identify and treat patients with long COVID and therefore Electronic Health Records (EHRs) of past COVID-19 patients could be used to help fill these knowledge gaps. We aimed to describe the incidence and differences in demographic and clinical characteristics in recorded long COVID in primary care records in England. With the approval of NHS England we used routine clinical data from over 19 million adults in England linked to SARS-COV-2 test result, hospitalisation and vaccination data to describe trends in the recording of 16 clinical codes related to long COVID between November 2020 and January 2023. Using OpenSAFELY, we calculated rates per 100,000 person-years and plotted how these changed over time. We compared crude and adjusted (for age, sex, 9 NHS regions of England, and the dominant variant circulating) rates of recorded long COVID in patient records between different key demographic and vaccination characteristics using negative binomial models. We identified a total of 55,465 people recorded to have long COVID over the study period, which included 20,025 diagnoses codes and 35,440 codes for further assessment. The incidence of new long COVID records increased steadily over 2021, and declined over 2022. The overall rate per 100,000 person-years was 177.5 cases in women (95% CI: 175.5–179) and 100.5 in men (99.5–102). The majority of those with a long COVID record did not have a recorded positive SARS-COV-2 test 12 or more weeks before the long COVID record. In this descriptive study, EHR recorded long COVID was very low between 2020 and 2023, and incident records of long COVID declined over 2022. Using EHR diagnostic or referral codes unfortunately has major limitations in identifying and ascertaining true cases and timing of long COVID. This research was supported by the 10.13039/501100000272 National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Background: Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk. Methods: We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997–2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids). Results: We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13–1.16], psoriasis 1.17 [1.15–1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1–1.12], psoriasis 1.21 [1.19–1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry. Conclusions: Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.

Dengue is a major health burden, but it can be challenging to examine transmission and evaluate control measures because outbreaks depend on multiple factors, including human population structure, prior immunity and climate. We combined population-representative paired sera collected before and after the 2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such factors influence transmission and control in island settings. Our results suggested the 10–19 year-old age group had the highest risk of infection, but we did not find strong evidence that other demographic or environmental risk factors were linked to seroconversion. A mathematical model jointly fitted to surveillance and serological data suggested that herd immunity and seasonally varying transmission could not explain observed dynamics. However, the model showed evidence of an additional reduction in transmission coinciding with a vector clean-up campaign, which may have contributed to the decline in cases in the later stages of the outbreak.